5, 10-seco-5, 19-cyclo-steroids of the androstane and pregnane series



5,l-SE(I0-5,19-CYbL6-STEROIDS OF. THEv ANDROSTANE AND PREGNANESERIES United States Patent 0 3,185,581 Patented May 25, 1965 "Ice ; acetate, aminoacet-ate, propionate, cyclopentylpropionate,

Lawrence H. Knox, Mexico City, Mexico, assignor to Syntax Corporation, Panama, Panama, a corporation of Panama 1 No Drawing. Filed June 11, 1963, Ser. No.'286,916 Claims priority, applicatign Mexico, Dec. 21, 1962,

'70, 72 22 Claims. '(Cl. 260-2395) This invention relates to novel cyclopentanopolyhydrophenanthrene derivatives and to processes for their preparation. More particularly, this invention relates to novel 5,l0-seco-5,19-cyclo steroids of the androstane and pregnane series represented by the general formulasz In these formulas, R represents the radical -OR or the radical wherein R represents a lower alkyl group, e.g., methyl, ethyl, propyl, butyl, and the like, or an acyl group containing up to 12 carbon atoms, R represents a lower alkyl group, an aryl group, e.g., phenyl and the like, or an aralkyl group, e.g., benzyl and the like, R represents hydrogen, a lower alkyl group, or an aryl or aralkyl group containing up to eight carbon atoms, and R and R taken together, along with the nitrogen atom to which they are attached, can also represent a heterocyclic radical such as piperidino, pyrrolidino, morpholino, piperazino, and

the like; Y represents hydroXyl or an ac'yloxy group-containing up to 12 carbon atoms; X represents hydrogen,- a lower alkyl group, a lower alkenyl group, e.g., vinyl and the like, or a lower alkinyl group, e.g., ethinyl and the like, and X and Y taken together can represent a keto group; R and R each represent hydrogen, hydroxyl or an acyloxy group containing up to 12 carbon atoms, R represents hydrogen, titmethyl, ,B-methyl or fl-hydroxyl; R and R taken together represent the grouping:

...O\ R1 ...O R8

wherein R represents hydrogen or'a lower alkyl group and R represents hydrogen, a lower alkyl group, an aryl group or an aralkyl group; X represents hydrogen or a halogen, e.g., fluorine or chlorine, and Y represents hydrogen, fi-hydroxyl or a keto group, with X and Y being hydrogen when R is hydrogen and X being hydrogen when Y is hydrogen. i

The acyl and acyloxy groups referred to hereinabove are derived from hydrocarbon carboxylic acids containing less than 12 carbon atoms. These. acids may be saturated or unsaturated, of straight, branched, cyclic or cyclic-aliphatic flrchloropropionate, enanthate and benzoate.

The compounds represented by Formula I hereinabove are anabolic agents having a favorable anabolic-androgenic ratio. They also exhibit anti-estrogenic and anti-gonadotropic activity, and lower blood cholesterol levels.

The compounds represented by Formula II wherein R is hydrogen are progestational agents which inhibit ovulation and relieve premenstrual tension, e

The compounds represented by Formula II wherein R is other than hydrogen and R is hydroxy are anti-inflam matory agents, useful in the treatment of rheumatism, arthritis, and inflammation of the skin, eyes, ears, and the like.

The novel 5,l0-seco-5,l 9-cyclo steroids represented by Formulas I and II can be obtained by methods such as those illustrated by the following reaction sequences, wherein for the sake of clarity only rings A and B of the steroid molecule are shown:

, In these formulas Rfi R and R have the same meanings as set forth hereinabove for Formulas I and II.

The starting material (A), a 5,10-methylene-l9-nor- A -3-keto steroid of the androstane or pregnane series, is obtained by reacting the corresponding l9-hydroxy-A 3 -keto steroid with an u-fluorinated amine as described in my copendingUS. patent application Serial No. 286,931, filed-on June 11, 1963. An illustrative but by no means exhaustive listing of 5,IO-methylene-l9-nor-A -3-keto-androstene and -pregnene starting materials includes 5,10-

chain, or aromatic, and may be substituted by functional groups such as hydroxyl, alkoxy containing up to 5 carbon atoms, acyloxy containing upto 12 carbon atoms, nitro,tamino, halogen, andthelike. Typical ester groups are the acetate, trimethylacetate, t-butylac'etate, phenoxy methylene- 19-nor-A -androstene-3,17-dione,

5,loqriethylene 19 nor-A -androsten-17p-ol-3-one and its 17-esters,

, 5,10-methyl-l7a-methyl-19-nor-A -androstenand the respective 21-monoesters of the aforementioned 2l-hydroxy compounds.

Reaction of the 5,10-methylene-19-norA -3-keto-androstene or pregnene starting materials (A) with a primary or secondary alcohol containing up to 8 carbon atoms, e.g., methanol, ethanol, propanol, isoamyl alcohol, cyclopentanol, cyclohexanol, and the like, produces the corresponding 3-alkoxy-5,1O-seco-5,19-cyclo-A -androstatriene or pregnatriene (B; R =lower alkyl). This reaction will generally be carried out at reflux temperature in the presence of an acid catalyst, such as p-toluenesulfonic acid, perchloric acid, sulfuric acid, and the like, for a period of time ranging from about 45 minutes to about 3 hours, and preferably for about 1 hour, with the primary or secondary alcohol reactant also serving as a solvent for the reaction.

Similarly, by reacting the 5,IO-methylene-d9-nor-A -3 keto-androstene or -pregnene starting material (A) with a hydrocarboxylic acid anhydride in the presence of an acidic catalyst, e.g., acetyl chloride, p-toluenesulfonic acid, or the like, preferably at a temperature ranging from room temperature (i.e., about 25 C.) to reflux temperature for from about 1'5 minutes to about 2 hours, the corresponding 3-acyloxy-5,10-seco-5,l9-cyclo-A -andmstatriene or pregnatriene (B; R =acyl) is obtained.

When carrying out this acylation reaction using starting materials which possess free primary or secondary hydroxyl groups, e.g., 5,1O-methylene I9-nor-A -androsten- 17/8-ol-3-one or 5,10-methylene19-nor-A -pregnen-2l-ol- 3,20-dione, the corresponding C 17 and/ or C-21 esters are always obtained. In the case of the 17B-hydroxy androstane derivatives substituted by a lower alkyl, alkenyl or alkinyl radical at the Na-position, or of corticoids which can be esterified at the 11- and/or 17-.position, it is recommended that the acylation reaction be effected at room temperature for a short time in order to avoid esterification of the tertiary hydroxyl group at the l7-p0sition and/ or the hydroxyl group at the ll-position.

Reaction of the 5,10-methylene-9-nor-A -3-keto-androstene or pregnene starting materials (A) with an ali phatic, cyclic or cyclic-aliphatic primary or secondary amine, e.g., dimethylamine, diethylamine, methylethylamine, aniline, methylaniline, pyrrolidine, piperidine, morpholine, piperazine, and the like, produces the corresponding 3-amino5,10-seco-5,l9-cyclo-A -androstatrienes and pregnatrienes (C). This reaction will be carried out in a solvent containing no active hydrogen, e.g., a hydrocarbon solvent such as benzene, toluene, xylene, and the like, and ether such as dioxane, diethyl ether, tetrahydrofuran, and the like, or a halogenated hydrocarbon such as methylene chloride and the like, as well as mixtures thereof, and in the presence of an acid catalyst, such as ptoluenesulfonic acid and the like, preferably at reflux temperature for a period of time ranging from about 60 minutes to about 4 hours.

The novel compounds of the present invention having free or esterified hydroxyl groups at various positions on od of Fried et al. [J. Am. Chem. Soc., Vol. 75, p. 2273 Various physical measurements, including nuclear magnetic resonance data indicate that the novel compounds of the present invention predominantly have the 5, 10-seco- 5,19-cyclo structure indicated in the formulas presented hereinabove. However, various chemical reactions, e.g., hydrogenation, indicate that these compounds can also exist in equilibrium with their electron tautomers, as shown by the following partial structural formulas:

N and extracted with ether.

Example I A mixture of 3 g. of SAG-methylene-19-nor-A -androstene-3,l7-dione, 250 cc. of methanol and 300 mg. of ptoluenesulfonic acid was heated at reflux temperature for 30 minutes. The mixture was cooled, diluted with water The extract was Washed with 4 sodium bicarbonate solution and water to neutral, dried over anhydrous sodium sulfate and evaporated to dryness. The residue was crystallized from methanol to give 3- methoxy 5,1O-seco-S,l9-cyclo-A -androstatrien-17- one which may be also designated as the tautomer 3-methoxy-5,l0 methylene-19-nor-A -androstadiene 17 one,

, ness under vacuo.

M.P. -'1-36 C.; [oc] +246 (CHCl Amax. 256-258 m log 6 3.76.

In a similar manner, starting from '5,lO-methylene-l9- nor-A -androsten l7B-o1-3-one there was obtained 3-methoxy-S,10-seco-5,l9-cyclo-A -androstatrien-l7/3-01 (3- methoxy 5,1O-methylene-19-nor-A -androstadien 01).

Example II A mixture 2.5 g. of 5,IO-methylene-19-nor-A -androstene-3,17-dione, 400 cc. of benzene, 2.5 g. of pyrrolidine and 250 mg. of p-toluenesulfonic acid was refluxed for 1 hour, diluted with water, the organic layer Was separated and washed with sodium bicarbonate solution and water to neutral, dried over anhydrous sodium sulfate and evaporated to dryness. Crystallization of the residue from methanol gave 3(N pyrrolidyl)-5, 10-seco 5;l9-cyclo- A P -andrOstatPien-I7-one (5,10-methylene 3(N-pyrrolidyl)-9-nor-A -androstadien-l7-one), M.P. 203-205" C.

Example III A mixture of 1 :g. of 5, 1O-methy-lene-l9-nor-A -androsten-l7/8-ol-3-one, 100 cc. of benzene, l g. of diethylamine and 100 mg. of p-toluenesulfonic acid was refluxed for 45 minutes cooled, washed to neutral and evaporated to dry- The residue was crystallized from methylene chloride-methanol, thus producing 3(N,N-diethylamino)-5,10-seco-5,l9-cyclo-A androstatrien- 175-01 (5,10-methylene-3 (N,N diethylamino) 19 nor- A -androstadien-175-01) Example IV In the method of the preceding example, diethylamine was substituted by dimethylamine, thus affording 3 (N,N- dirnethylaminol)-5,10-seco-5,19 cyclo A andro statrien-17fi-ol (5,10-methylene-3 (N,N dimethylamino)- l9-nor-A -androstadien-17/3-01) A mixture of 500 mg. of the foregoing compound, 4 cc. of pyridine and 4 cc. of acetic anhydride was kept at room temperature over night; it was poured into water and the formed precipitate filtered off, to give the acetate of 3 (N,N-dimethylamino)-5,10-seco 5,19 cyclo A androst-atrien-UB-ol, (acetate of 5,lO-methylene-3 (N,N- dimethylamino)-l9-nor-A -androstadien-175-01),

' Example V A solution of 5 g. of 5,1O-methylene-19-nor-A -androsten-17B-ol-3-one in 50 cc. of acetic anhydride and 5 cc. of acetyl chloride was refluxed'for 15 minutes under 'nitrogen atmosphere. The reaction mixture was distilled almost to dryness,cooled, diluted with ether, and the organic extract Washed with Water, thenwith 5% sodium bicarbonate solution and finally with Water, dried and evaporated .to dryness. There was thus obtained 3,17- diacetoxy-5,lO-sec'-5,19 cyclo A androstatriene- 6 Example VIII By following the method described in Example I, 2 g. of 5,1O-methylene-19-nor-A -pregnene-17a,21-dio1-3,11,20- trione were converted into S-methoxy 5,10 seco 5,19-

7 cyc10-A pregnatriene-17a,21-diol 11,20 dione (3- (3,17-diacetoxy-5,10-methylene 19 9 nor A androstadiene). I

By the same method, the compounds below mentioned (I) were converted into (11).

r II

. 3-acetoxy-5,10seco-5,IQ-eyelo- (3-acetoxy-5,10-methy1ene-19-nor- A -pregnadien-20-one.)

3-aeetoxy-17a-methyl-5,10-seco-5,

19-cyclo-A -androstatrie11- (3-acetoxy-5,10-methylene-17amethyl-IQ-nor-AL -androstadien- 3-acetoxy-17a-ethinyl-5,10-seco-5, l9-cyelo-A (10) r -androstatrien- (3-acetoxy-5,IO-methyIen-UQ- ethinyl-lQ-nor-A -androstadien- 3-acet0xy-16a-methy1-5,10-seeo-5,

19-eyc1o-A -pregnatrien- 20-one.

, (3-acetoxy-5,IO-methylene-lGumethyl-19-nor-A -pregnadien- 5,10-methy1ene-19-nor- A pregnene.-3,20-dione.

5,10-methylene-17 t-methyl-19- nor-A -androsten-17fl-ol-3-one.

5,10-methylen-17a-ethinyl-lQ-nor- A -androsten-17B-ol-3-one.

5,10-methylene-16a-methy1-19'n0r- A -pregnene-3,20-dione,

20-one). 3,21-diacetoxy-5,10-seco-5,19-eyclo- 1 -pregnatrien-17a-o1-20- one. (3,2l-diacetoxy-fi,10-methylene-19- nor-A1- -ptegnadien-17a-ol-20- one).

3-acetoxy-5,10-seco-5,19-cyc1o- A Z, -pregnatrien-lla-ol-ZO- one) (3-acetoxy-5,10-methy1ene-19-nor- A -pregnadien-l7a-ol-20-one) 3,l7-diaeetoxy-5,10-see0-5,19-cyelo- A (10) -pregnatrien-20mne. I (3,IT-diacetoxy-fi,lo-methylene 19- nor-A -pregnadien-2O-one) 3-acetoxy-16fl-methyl-5,10-seco-5,

19-cyclo-A -pregnatrien- 20-onc. V

(3-acetoxy-5,10-methylene-16B- methyl-IQ-nor-A -pregnadien- 20one):

5,10-methylene-19-nor-n -pregnone-17a, 21-di0l-3,20-d1one-21 acetate.

5,10-methylene-l9-nor-A -pregnenl7a-o1-3,20-dione.

5,10-methylene-lQ-nor-N-pregnen- 17x-01-3,20-(1i0118 acetate.

Example VI In the method of Example I, methanol was substituted by ethanol, isopropanol and isoamyl-alcohol, to produce, using 5,1O-methylene-19-nor-A androsten-17fi-o1-3-one as starting material, 3-ethoxy-5,10-seco-5,19cyclo-A androstatrien-17B-ol (3-ethoxy-5,10 methylene 19 nor- A -androstadien-175-01), 3-isopropoxy-5,1O seco 5,19- cyclo-A -androstatrien-17/3-01, (3 isopropoxy 4 5,10- methylene-19-n0r-A -androstadien 1713 01) and 3 '-isoamylbxy-S,10=seco-5,19-cyclo-A -androstatrien 175- ol-(3-isoamyloxy-5,10-methylene-19-nor A androstadien-llfi-ol).

Example VII In accordance with the methoddescribedin' Example I,

5,IO-methylenee19-nor-A -pregnene-3,ZO dione and 5,10-' methylene-19-nor-Al pregnene-17 cull-$013,20 dione 21- acetate were converted into 3-methoxy-5,10-seco=5,19-'

cycle-A -ptegnatrien-20-one (3-'methoxy-5;10-meth I ylene-l9-nor-A -pregnadienaO-one) and 3-meth0xy-5,'10-

seco-5,19-cyclo-A -pregnatrien-l'la,21-diol 20 one ill-acetate (3-meth0xy-5,lO-methylene-l9 nor-A -pregnadiene-17u,21-diol-20-one ZI-acetate).

methoxy-S,1O-methylene-l9-nor-A -pregnadiene 1704,21- dio1-11',20-dione) which was acetylated with acetic anhydride in pyridine in accordance with the method described in Example 1V.

III-,the same manner, starting from 5,10-methylene-19- n0r-A -pregnene-11B,17a,21-tri01- 3,20 dione there were obtained 3-met-hoxy-5,10seeo 5, 19-cyclo A -pregnatriene-l1fi,17oc,Z1-triol-20-One (3-methoxy-5,IO-rnethyIene- 19no1'-A '-pregnadiene-1lfl,17a,21-trio1-20-one) and its 21-acetate. l 4

Exahipl e IX r tate of= 3-cyclopentyloxy-5,10-seco-5,19-cyclo-A p regnatrien-17oc-o1-20-one (the acetate of 3-cyclopentyloxy-5,10-methylene l9 nor-A r -pregnadien 17u-0l-20- one) and the 21-aeetate of 3-cyclopentyloxy-16u-methyl- 5,10-seco-5,19 cyclo-A -pregnatrien 17oc,21 diol- 20-one (21-acetate of 3-cyelopentyloxy-5,IO-methylene- 16a-methyl-19-nor-A -pregnadiene-1 7a,21-diol-20-one) Example X To a solution of 1 g. of 5,10-methylene-19-nor-A pregnene-3,20-dione in 75 cc. in ethanol there was added 0.5 cc. of 72% perchloric acid and the mixture was refluxed for 1 hour. It was then diluted with water,

extracted with ether and the organic extract washed to neutral, dried and evaporated to dryness. The residue Was crystallized from acetone-ether, thus affording 3-ethoxy-5,10-seco 5,19-cyclo-A -pregnatrien-20-one (3- ethoxy-S, IO-methylene-19-nor-A -pregnadiene-20-0ne) In the same manner 5,10-methylene-17 a-methyl-19-nor- A -androstene-l7/3-ol-3-one, 5,l0-methylene-17a-vinyl-19- nor-d -androsten-17fi-ol-3-one and 5,10-methylene-17otethinyl-19-nor-A -androsten-17B-o1-3-one were converted respectively into 3-ethoxy-17a-methyl 5,10 seco-5,19 cycle-A -androstatrien-l7fl-ol (3-ethoxy-5,10-methylene-l7a-methyl-19-nor-A -androstadien-175-01), 3-ethoxy-17a-vinyl- 5,10 seco 5,19 cyclo-A -androstatrien-17fi-ol (3-ethoxy-5,10 methylene-17a-vinyl19-nor- A -androstadien-17 3-01) and 3-ethoxy-17ot-ethinyl-5,10- seco 5,19-cyclo-A -androstatriem-01 (3-ethoxy- 5,10-methylene 17cc ethinyl 19 nor-Am-androstadien- 7 Example XI By following method described in Example III the compounds below mentioned (I) Were treated with primary or secondary'amines toproduce the compounds listedunder II. 1

Example XIV In the method of Example III benzene was substituted by toluene, to produce also 3(N,N-diethylamino)-5,10- seco-S,19-cyclo-A -and:rostatrien-173-01 (5,10-methylene-3 (N,N diethylarnino) 19 nor A androstadien- 175-01) in similar yield. I

'Example XV Example III was repeated but using dioxane as solvent,

to produce the same product in similar yield.

Example X V1 stirred at C. for 1 hour under nitrogen atmosphere, the

mixture was neutralized with acetic acid and the methanol Was distilled under reduced pressure. triturated with water, the solid was filtered off, washed with water, dried and recrystallized from ethyl acetatemethanol, thus producing 3(N-methylanilino)-5,10-sec0- 5,19 cycle-A -pregnatriene-17a,2l-diol-11,20-di0ne (5,10 methylene-3 (N-methylanilino)-19-nor-A -pregnadiene-17a,21-dio1-1 1,20-dione) In the same manner 3 (N-ipethyl, N-ethylamino)-9ofiuoro-5,1O-seco-5,19-cyclo-A -pregnatriene-11,8,17a, 2l-triol-20-one 2l-acetate (9a-fiuoro-5,10-methylene-3 (N- methyl, N ethylamino)-19-nor-A -pregnadiene-l1,8,17a, 2 l-triol-ZO-one 21-acetate) 3 (N-pyrrolidyl)-5,1 0-seco-5, 19-cyclo-A 3 -pregnatricne-l7u,2l-diol-20-one 21-acetate (5,10-methylene-3 (N-pyrrolidyl-19nor-A -pregnadiene-17a,2l-di01-20-one Zl-acetate) and 3(N-pyrrolidyl)- 16o:,17oc isopropylidenedioxy 5,10 seeo 5,19 cyclo- A -pregnatrien-21-ol-11,20-dione acetate (5,10-moth! ylene 3(N pyrrolidyl)-16o:,l7a-isopropylidenedioxy 19- nor-A -pregnadien-21-ol-11,20-dione acetate), were con verted into the corresponding free compounds.

Example XVII ing the respective esters.

Example XVIII A mixture of 1 got the acetate of 5,10-methylene 1'9 n -androsten-17,8-01-3-0ne, cc. of propionic anhydride and 100 mg. of p-toluenesulfonic acid was refluxed tor The residue was r 1 hour, it was poured into sodium carbonate solution and Y stirred for 30 minutes to hydrolyze the excess. anhydride.

methyl 19-nor-A -androstem17I3-o1-3-one there was obtained 3,175 dipropionoxy-17a-rnethyl-5,10-seco-5, 19-

10 cycloA -androstatriene (5;IO-methylene-lh-methyl- 3 17 fl-dipropionoxy19-nor-A -androstadiene) I claim: 1. A compound selected from the group consisting of compounds'represented by the formula:

wherein R is selected from the group consisting of OR and Rs eN/ R being selected from the group consisting of a lower alkyl group and an acyl group containing up to 12 carbon atoms, R being selected from the group consisting of a lower alkyl group, a monocyclic aryl group and a rnonocyclic aralkyl' group, and R being selected from the group consisting of hydrogen, a lower alkyl group, an aryl group containing up to 8 carbon atoms and an aralkyl group containing up to 8. carbon atoms, with R and R taken together, along with the nitrogen atom to which they are attached, being a heterocyclic group selected from the group consisting of piperidino, pyrollidino, rnorpholino and piperazino; X is selected from the group consisting of hydrogen, a lower alkyl group, a lower alkenyl group and a lower alkinyl group, and Y is selected from the group consisting of hydroxyl and an acyloxy group containing up to 12 carbon atoms; with X and Y taken together being a keto group.

2. 3 methoxy-SJO-seco-S,l9-cycloA -androstatrien-17-one.

3. 3 methoxy-S,Ill-methylene-19-nor-A -androstadien-17-one.

4. 3,17 diacetoxy 5,1O-seco-S,19-cyc1o-A -androstatriene.

5. 3,17 diacetoxy-S,1O-methylene-19-nor-A -androstadiene.

6. 3(N pyrrolidyl)-5,IO-seco-S,19-cyc1oPA -androstatrien-17-one.

7. 5,10 methylene-3 (N-pyrrolidyl)-19-nor-A androstadien-17-one.

' 8. 3(N pyrrolidyl.)e5,10-secoe5,l9-cyclo-A -androstatrien-l7fl-ol.

9. 5,1 0 methylene-3 (N-pyrrolidyl) -19-nor-A -androstadien-l7 8-ol. I

10. 3(N,N dimethy1amino) 5,10 seco 5,19 cyclol 11., 5,10 methylene 3(N,N-dimethylamino)-19-norn -androstadien--01. l

and compounds represented by the formula:

wherein R is selected from the group consisting of -OR and R being selected from the group consisting of a lower alkyl group and an acyl group containing up to 12 carbon 7 atoms, R being selected from the group consisting of a lower alkyl group, a monocyclic aryl group and a monocyclic aralkyl group, and R being selected from the group consisting of hydrogen, a lower alkyl group, an aryl group containing up to 8 carbon atoms and an aralkyl group containing up to 8 carbon atoms, with R and R taken together, along with the nitrogen atom to which they are attached, being a heterocyclic group selected from the group consisting of piperidino, pyrollidino, morpholino and piperazino; and R is selected from the group consisting of hydrogen, hydroxyl and an acyloxy group containing up to 12 carbon atoms, and R is selected from the group consisting of hydrogen, a-methyl, fl-methyl and ,B-hydroxyl, with R and R taken together beingwherein R is selected from the group consisting of hydrogen and a lower alkyl group and R is selected from the group consisting of hydrogen, a lower alkyl group, a monocyclic aryl group and a monocyclic aralkyl group. 13. 3 methOXy-S,l0-seco-5,l9-cyclo-A -pregnatrien-ZO-one. v I i 14. 3 acetoXy-5,l0-seco-5,19-cyclo-A pregnatriemZO-one. 15. 3(N pyrrolidyl) 5,10-seco-5,19-cyclo-A pregnatrien-ZO-one.

16. 3(N methylamino)-5,1,0 seco-5,l9-cyclo nli pregnatrien-17aol-20-one.

i2 17. A compound selected'frorn the group consisting of compounds represented by the formula:

CHZORQ V and compounds represented by the formula:

CHzOR R being selected from the group consisting of a lower alkyl group and an acyl group containing up to 12 carbon atoms, R being selected from the group consisting of a lower alkyl group, a monocyclic aryl group and a monocyclic aralkyl group, and R being selected from the group consisting of hydrogen, a lower alkyl group, an aryl group containing up to 8 carbon atoms and an aralkyl group containing up to 8 carbon atoms, with R and R taken together, along with the nitrogen atom to which they are attached, being a heterocyclic group selected from the group consisting of piperidino, pyrollidino, morpholino and piperazino; R is selected from the group consisting of hydrogen, hydroxyl and an acyloxy group containing up to 12 carbon atoms; R is selected from the group consisting of hydrogen, a-methyl, fi-methyl and B-hydroxyl, with R and R taken together being wherein R is selected from the group consisting of hydrogen and a lower alkyl group and R is selected from the group consisting of hydrogen, a lower alkyl group, a monocyclic aryl group and a monocyclic aralkyl group; R is selected from the group consisting of hydrogen and an acyl group containing up to 12 carbon atoms; X is selected from the group consisting of hydrogen and a halogen, and Y is selected from the group consisting of hydrogen, ,B-hydroxyl and a keto group, with X being hydrogen when Y is hydrogen.

18. 3 methoxy-S,lO-seoo-S,l9-cyclo-A -pregnatriene-l lfi,17 z,21-triol-20-one.

19. 3(N pyrrolidyl) 5,10-seco-5,19-cyclo-A pregnatriene-17a,21-diol-l1;20-dione Zl-acetate.

20. 3(N methyl-N-ethylamino)-9ot-fluoro-5,10-seco- 5,19 cyclo-A -pregnatriene-11p,17a,21-trio1-20-one ZI-acetate.

21. 3(N piperidyl)-5,10-seco-5,l9-cyclo-A -pregnatriene-17a,21-diol-11,20-dione.

22. 3(N pyrrolidyl)-16a,17a-isopropylidenedioXy-5, .l0-seco-5,19-cyclo-A -pregnatrien-21-ol-11,20-dione.

V s No references cited. LEWIS GOT TS, Primary Examiner. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS REPRESENTED BY THE FORMULA: 